1. Field of the Invention
This invention relates to treatment of herpes virus infections. More specifically, it concerns treatment of such infections with N,N'- diacetylcystine, N-acetyl homocysteine and N-acetylcysteine by interfering with leukotriene production.
2. General Background of the Invention
The large family of viruses known as the herpes viruses attack the skin and mucous membranes to produce both local eruptions and ulcers as well as generalized systemic symptoms of infection such as headaches, fever and malaise. The most common herpes viral infections are with herpes homonis simplex I and II.
There are generally two types of herpes infection viruses. Those produced by the herpes simplex are characterized by the eruptions of one or more groups of vesicles or sores on the human body, especially on the vermillion border of the lips, at the external nares, on the glans, prepuce or vulva.
Herpes simplex virus type 1 is known as the "skin" or "above the umbilicus" virus and type 2 is known as the "genital"or "below the umbilicus" virus. The types cannot be distinguished in a culture, but can be distinguished on the basis of the antibodies generated upon exposure to the virus. The two types cross react with one another in the laboratory and are, thus, very closely related to each other.
Herpes infections have been called, according to their sites, fever blisters, cold sores, herpes catarrhalis, herpes facialis, herpes febrilis, herpes genitalis, herpes labialis, herpes mentalis, herpes preputialis, herpes progenitalis, intrauteine herpes, etc. The infection is commonly recrudescent and reappears during other febrile illness or even physiological states such as menstruation and high stress.
Those lesions produced by herpes zoster develop along nerve sheaths with eruptive lesions in a linear patterns along dermal distributions of nerves on the face, trunk, abdomen, and extremeties producing extremely painful, eruptive, weeping lesions that heal extremely slowly with paraphesia. This type of infection is known as shingles and is seen in patients with cancer and opportunistic debilitating infections that depress the immune system of the patient.
Various treatments for herpes hominis simplex have been proposed. Asculai, U.S. Pat. No. 4,147,803, reports that certain sorbitan derivatives have antiherpetic activity. DeLong et al., (U.S. Pat. No. 3,639,612) described such activity for certain chalcogen containing heterocyclic compounds. Stedman, (U.S. Pat. No. 3,555,355), discloses that certain cycloalkylamines have activity against herpes simplex as does cycloheximide, (U.S. Pat. No. 4,427,684). Fleming et al., (U.S. Pat. No. 3,829,578), teaches that certain bis-basic ethers and xanthen-9-ones have anti-viral activity and Soichet, (U.S. Pat. No. 4,312,884), describes such antiviral activity by Spectinomycin.
Kaufman et al., (Arch. Ophthalmol. 68: 235-239 (1962)), reported treatment of herpes simplex keratitis with 5-iodo-2-deoxyridine (IUD). Schabel describes treatment of genital herpetic infection with 9-beta-D-arabino-fluranosyl adenine (Chemotherapy 13: 321-338 (1968)), and reported antiviral activity of 5-tri-fluoromethyl-2-deoxyuridine, (N.Y. Acad., Sci. 130: 168-180 (1965)). Adams et al., (J. Infect. Dis. 133 (suppl) 151-159 (1976)), treated genital herpes infections with topical application of adenine arabinside. Felber et al., (JAMA 223: 289-292 (1973)), described treatment of herpes infections by application of a vital dye as neutral red or proflavine followed by exposure to light. Chese-man et al., (N. Eng. J. Med. 300: 1345-1349 (1979)), and Pazin et al., (N. Engl. J. Med. 301: 225-230 (1979)), report the treatment of herpes simplex infection by human leukocyte interferon. Blough and Giuntoli, (JAMA 241: 2798-2801 (1979)), described treatment of human genital herpes infections with 2-deoxy-D-glucose. Schaeffer et al., (Nature 272: 583-585 (1978)), Fyfe et al., (J. Biol. Chem. 253: 8721-8727 (1978)), Sely et al., (Lancet 2: 1257-1270 (1979)), Park et al., (J. Infect. dis. 140: 802-806 (1979)), and Pavan-Langston et al., (Am J. Ophthalmol. 86: 618-623 (1978)), reported treatment of herpes infections by 9-(2-hydroxyethoxymethyl)guanine (Acyclovir). Fisher (Cutis 29: 467-472 (1982)), described treatment of herpes simplex infections with Amantadine Hydrochloride. Other forms of treatment of herpes hominis simplex Type I and II include a variety of agents such as lysine, ascorbic acid, topical ether and topical chloroform, thymol, nonionic surfactants, (U.S. Pat. Nos. 4,147,803, and 4,185,097) inactivated herpes viruses, zinc, urea, tannic acid, (U.S. Pat. No. 4,285,934), glutaraldehyde, cow pox vaccine, intradermal injections of gamma globulins, and a surgical treatment by epidermal excisions of the herpetic lesions.
Recently a mixture of L-lysine, gibberellic acid and urea has been reported to be useful in the treatment of H. simplex (U.S. Pat. 4,424,232). Similarly, transfer factor has been reported to be useful in the treatment of herpes simplex (U.S. Pat. No. 4,435,384). Adenosine monophosphate has recently been reported to reduce pain and increase healing of herpes zoster lesions (JAMA).
None of these prior art methods have proved satisfactory in treating skin ulcers caused by herpes virus-infections. If is accordingly the principal object of the present invention to provide a new method of treating herpes simplex by topical administration of a medication having good activities against herpes simplex and zoster and which further acts very quickly to effect essentially total relief of pain from the affected area.
These and other objects and advantages of the invention will become apparent from the following description.